Previously known methods for preparing optically active β-amino acids include those in which racemates of the desired β-amino acids are first prepared and then optically resolved by using either optically active resolving agents or enzymes and those by asymmetric synthesis.
For example, non-patent reference No. 1 reports a method for producing an optically active β-amino acid derivative by reacting an aromatic secondary amine with an enone in the presence of a chiral Lewis acid.
However, such method has problems of that, for example, it requires a deprotection process to remove the alkyl group on the amino group of the obtained optically active β-amino acid derivatives, to obtain the desired product, because it makes use of secondary amines as the starting material.
Non-patent reference No. 2 reports, on the other hand, a method for the production of β-amino acids by addition of morpholine to crotonic acid esters.
However, the method also has problems of that the β-amino acids obtainable are racemates and no optically active compounds have obtained. In addition, the report says that no addition reaction product was obtainable when 3,5-bis(trifluoromethyl)aniline was made to react with cyanoolefines.
Non-patent reference No. 4 reports a method for producing β-amino acid derivatives by reacting an α,β-unsaturated carboxylic acid derivative with a primary or secondary amine in the presence of a diphosphine-palladium catalyst.
However, the non-patent reference No. 4 has neither description of trial on an asymmetric reaction nor that of optical purity of the β-amino acids obtained.
Non-patent reference No. 5 reports a method for producing β-amino acid derivatives by reacting an α,β-unsaturated carboxylic acid derivative with a primary amine in the presence of a BINAP-palladium catalyst.
However, although it has description about optical purities of the β-amino acids obtained, it has no indication of R- or S-form. Furthermore, when amines of a high nucleophilicity, for example, methoxyaniline, etc. are used, only products of low optical purities are obtained.
The non-patent reference No. 3 and patent reference No. 1 also report a method for producing β-aminoamides using a chiral Lewis acid. This method, however, is not satisfactory as an industrial production, on the one hand, because it has to be carried out practically at temperatures as low as −60° C., resulting in operational difficulty, and, on the other hand, at higher temperatures, although the yields are improved but the optical purities are thought to be lowered. Another problem in the method is that it requires more than catalytic amount, for example, more than 30 mol % of the chiral Lewis acids.
Non-patent reference No. 6 describes a method in which lithium amides are reacted with α,β-unsaturated carboxylic acid esters in the presence of chiral ligands. However, the method still has problems and is not industrially applicable one, because it requires lithiation of the amine used at very low temperature of −78° C. in order to obtain product of a high optical purity, and a chiral ligand is used in an amount of not less than one equivalent.
Non-patent reference 1: Chem. Commun., 1240 (2001).
Non-patent reference 2: Chem. Commun., 30 (2003).
Non-patent reference 3: J. American Chemical Society, 120, 6615 (1998).
Non-patent reference 4: J. Organometallic Chemistry, 665, 250 (2003).
Non-patent reference 5: Chem. Commun., 1132 (2003).
Non-patent reference 6: J. American Chemical Society, 125, 2886 (2003).
Patent reference 1: U.S. Pat. No. 6,080,857.